9-112268162-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001163788.4(PTBP3):​c.238G>A​(p.Val80Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,611,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V80A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PTBP3
NM_001163788.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.828
Variant links:
Genes affected
PTBP3 (HGNC:10253): (polypyrimidine tract binding protein 3) The protein encoded by this gene binds RNA and is a regulator of cell differentiation. The encoded protein preferentially binds to poly(G) and poly(U) sequences in vitro. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.049712867).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTBP3NM_001163788.4 linkuse as main transcriptc.238G>A p.Val80Ile missense_variant 4/14 ENST00000374257.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTBP3ENST00000374257.6 linkuse as main transcriptc.238G>A p.Val80Ile missense_variant 4/142 NM_001163788.4 P1O95758-6

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000404
AC:
10
AN:
247734
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000895
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000548
Gnomad SAS exome
AF:
0.000102
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1458812
Hom.:
0
Cov.:
30
AF XY:
0.0000179
AC XY:
13
AN XY:
725606
show subpopulations
Gnomad4 AFR exome
AF:
0.0000601
Gnomad4 AMR exome
AF:
0.000160
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.0000952
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 01, 2022The c.331G>A (p.V111I) alteration is located in exon 1 (coding exon 1) of the PTBP3 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the valine (V) at amino acid position 111 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.030
.;.;.;T;.;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.71
T;T;T;T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.050
T;T;T;T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
-0.91
.;.;.;N;.;.
MutationTaster
Benign
0.68
D;D;D;D;D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.62
N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.33
T;T;T;T;T;T
Sift4G
Benign
0.24
T;T;T;T;T;.
Polyphen
0.020
B;B;.;B;.;.
Vest4
0.17
MutPred
0.30
.;.;.;Loss of catalytic residue at V108 (P = 0.0469);.;.;
MVP
0.39
MPC
0.10
ClinPred
0.075
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs556943992; hg19: chr9-115030442; COSMIC: COSV52957718; COSMIC: COSV52957718; API